The effects of drugs on the size of the pupil is among the most easily detected and characteristic signs of drug action. Several animal studies conducted at the ARC have clarified the neural mechanisms through which psychoactive drugs influence pupil diameter and the light reflex. This research has been extended to clinical studies where the pupillary effects of several classes of abused drugs were compared to their performance and subjective effects. Additional research on retinal physiology using newly developed pupillometers has yielded new information of the retinal processing of the light reflex. Since retinal neural organization mimics brain neural systems, it is proposed that the influence of drugs in this system indicates drug mechanisms elsewhere in the brain. Dependent measures of these studies include pupil size, constriction and dilation velocities of the light reflex, smooth pursuit and saccadic tracking. These studies are typically within subject repeated measure design, when drugs are administered it is double blind and placebo controlled. Progress to date: The effects of marijuana, ethanol, cocaine, opiates amphetamine have been studies after various routes of administration.